Marked reduction in myeloma bone disease and tumor burden in vivo as a result of functional blockade of MIP-1α bioactivity with neutralizing antibodies to MIP-1α (A) Treatment schedule. (B) Neutralization of MIP-1α bioactivity significantly inhibited the development of osteolytic lesions and reduced skeletal tumor volume in myeloma-bearing mice. Left panel: anti-MIP-1α antibodies significantly reduced the number of osteolytic lesions compared with treatment with isotype IgG_2a and PBS (number in parentheses represents mice with at least one lesion per mouse in group). Right panel: the anti-MIP-1α antibodies also significantly reduced the proportion of the marrow cavity occupied by tumor in bones of the hind limbs compared with treatment with isotype IgG_2a or PBS (P = .0011). (C) Treatment with anti-MIP-1α antibodies resulted in a significant reduction in incidence of splenomegaly in myeloma-bearing mice (• indicates values for individual mice treated with anti-MIP-1α antibodies; ○, values for control mice that received isotype IgG or vehicle). All control mice had significantly enlarged spleens (at least 0.3 g), whereas only 4 of 10 mice that received anti-MIP-1α antibody had splenomegaly (normal non-tumor-bearing mouse spleen, 0.1 g or less). There was a positive correlation between splenic wet weights and serum IgG_2bκ levels (r = 0.83). (D) Treatment with anti-MIP-1α antibodies significantly reduced serum IgG_2bκ titers in 7 of 10 tumor-bearing mice (5.45 ± 1.56 mg/mL), below the median for the pooled controls (9.26 mg/mL); line, median; box, 25% to 75%; bar, 95% confidence interval (“Statistical Analysis”).